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2. Luteal phase support in ART
Aboubakr Elnashar
Benha university Hospital, Egypt

3. WHY? Abnormal luteal function after COS for IVF Suppression of LH
Continued down-regulation by GnRHa
Removal of of granulosa cells at OR
Supra physiological E2/P4 in early luteal phase
hCG injection before OR

4. 3. WHEN TO START?
From day of OR
Not be later than day 3 after OR

5. 4. WHEN TO STOP?
Minimum:
14 days from the day of ET until the day of a positive HCG test.
(Andersen et al., 2002)
18 days following OR
(Mochtar et al., 2006)
8-10 w of gestation
1st T:
delaying miscarriage but not improve LBR
(Andersen et al, 2002, Aboulghar et al, 2008)

6. 5. WHAT TO USE FOR LPS?
hCG
Progesterone

7. HCG: Rescue corpus luteum
(Hutchins Williams et al. 1990)
improves the implantation by increasing relaxin, integrin & placntal ptn
(Mochtar, 1998)
increase the risk of OHSS
(van der Linden et al., 2012)

8. Progestagen in Egyptian market
Company
Price
(LE)
Form Mg
Generic name
Trade name
Abbott 36
20 tab 10
Dydrogesterone
Oral
Duphaston
Ibsa
105
10 amp
100
Progesteron IM
Prontogest 72
30 vag pessaries
200
Vag or rectal
102
400
Actavis 90
15 vag pessaries
Cyclogest
125
Ferring
21 vag tab
Vag
Endometrin
Serono
236
jell15 tube
8 %
Progesterone
Crinon
Octoper 29
30 caps
Vag or oral
Uterocare
Pharco 21
24 caps
Progest
adwia
progesterone
Oral only
cyclotron
Globe 22
15 caps
Hysterogest

9. Only 10% of oral dose circulates as active P4 {first pass effect}
1. Oral progesterone
Micronized:
Only 10% of oral dose circulates as active P4
{first pass effect}
No secretory transformation of the endometrium in patients with POF who had been treated with oral micronized progesterone
(Devroey et al.1989; Bourgain et al. 1990)

10. Retro steroid progesterone (dydrogesterone)
Better oral bioavailability
Rapidly absorbed: maximal levels: 30 min- 2.5 h
Mean terminal half life: 5-7 h
Fast and stable effect
Its metabolites have progestogenic activity.
Requires a 10–20 times lower oral dose than micronized progesterone

11. 2. IM progesterone
Serum P4 levels well above the physiological range with adequate endometrial secretory changes
Dose:
natural progesterone in oil, 25 and 100 mg/d: No significant difference in outcome
(Costabile et al., 2001, Pritts & Atwood, 2002)

12. Side effects: painful injections inflammatory reactions rash
needs to be administered by nurse
(Lightman et al., 1999)

13. 3. Vaginal progesterone
“Targeted drug delivery” from vagina to uterus: better endometrial histology
High uterine progesterone concentrations {anatomically close blood vessels: uterine first pass effect}
(Cicinelli et al., 2000, de Ziegler et al., 1995)

14. Comparing routes of progesterone administration
IM progesterone to have more effect on CPR than oral and vaginal or rectal progesterone, but none of these results were significant.
(Cochrane SR, 2011)

15. Micronized progesterone Vs synthetic progesterone
Oral:
Micronized progesterone Vs synthetic progesterone
significant benefit from synthetic progesterone
(Peto OR 0.79, 95% CI 0.65 to 0.96).
Significant effect in favour of synthetic progesterone compared to micronized progesterone.
The only synthetic progesterone used was oral dydrogesterone
(Cochrane SR, 2011)

16. Both are equally effective
Vaginal
Gel or capsules ?
Both are equally effective
(Daya & Grundy, 2004)
Capsule more cost effective than gel: Gel is 4 times more expensive than Capsules
(Elenany et al, 2011)
No difference in CPR between gel and all other vaginal preparations
(MA: Polyzoz et al, 2010)

17. 4. Rectal application
: serum concentration during the first 8h twice as high as other forms.
no prospective RCT to compare the rectal with other administration routes for IVF
(Chakmakijan & Zachariah, 1987)

18. 5. SC
A new water-soluble progesterone
Implantation rate, PR, LBR and early miscarriage rate for Prolutex were similar to those for Crinone.
The adverse event profiles were similar and Prolutex was safe and well tolerated.

19. IM P for the Highest Serum levels and
For IDEAL LPS:
IM P for the Highest Serum levels and
Vaginal P for increasing the Endometrial levels
Until Placental progesterone production adequate, around week 8-10 w of gestation.
(Fert.Steril, 2012)

20. 6. CO-TREATMENTS TO PROGESTERONE 1
6. CO-TREATMENTS TO PROGESTERONE 1. Addition of E2 to progesterone No effect of oral estrogens (van der Linden et al., 2012) Transdermal estrogen is beneficial (Cochrane SR, van der Linden et al., 2012) No effect in antagonist protocol

21. doesn’t improve ovarian responsiveness, blood flow, and PR
2. Low dose aspirin
VD and decreased platelet aggregation increased ovarian and endometrial blood flow  ovarian responsiveness,  endometrial thickness,  IR
Decrease uterine contraction at the time of ET
doesn’t improve ovarian responsiveness, blood flow, and PR
(Dirckx et al., 2009; Lambers et al., 2009)

22. 3. Piroxicam Doesn’t improve PR An oral dose 10 mg 1-2 h before ET
significantly improves PR
(Moon., 2004)
Doesn’t improve PR
(Dal and Borini, 2009)

23. does not improve PR in oocyte recipients
4. Indomethacin
100 mg q12h rectally for 3 doses from the night before ET
does not improve PR in oocyte recipients
(Bernabue, 2006)

24. 4. low dose heparin did not improve PR or IR
5000 IU bid and aspirin 100 mg/day from the day of ET
did not improve PR or IR
(Stern et al., 2003)

25. 5. Prednisolone does not increase PR 10 mg/d before or after ET
(Ubaldi et al., 2002)

26. 6. Viagra
25 mg qid vaginally from stimulation D1 to hCG day (Sher, 2002; Paulus,2002)

27. 7. Ascorbic acid
Luteal regression is associated with ascorbate depletion and the generation of reactive oxygen species, which inhibit the action of LH and block steroidogenesis
No value
(Griesinger et al.,2002)

28. 8. GnRHa in midluteal phase
Rationale:
GnRH receptor is expressed in
preimplantation embryos
Endometrium
corpus luteum
GnRHa stimulate trophoblast production of hCG

29. Triptorelin 0.1 SC (or 0.5 mg Leuprolide acetate) 6 days after ICSI
Dose:
Single dose:
Triptorelin 0.1 SC (or 0.5 mg Leuprolide acetate) 6 days after ICSI
(Tesarik et al., 2006; Ata et al., 2008; Isik et al., 2009; Razieh et al., 2009)
Multiple doses:
Triptorelin: daily 0.1 mg SC until day of beta-HCG or 14 days after OR
(Fujii et al., 2001; Isikoglu et al., 2007, Abouelghar et al, 2015)
Which GnRHa is more beneficial?
No differences
(van der Linden et al., 2012)

30. You can get: This lecture from: My scientific page on Face book:
Aboubakr Elnashar Lectures.
Slide share web site
All lectures from:
My clinic, 3 Althawra St. Almansura